T099: High efficacy and durability of second-line therapy with pembrolizumab, gemcitabine, vinorelbine, and liposomal doxorubicin in the phase II study for relapsed and refractory Hodgkin lymphoma
Authors: Alison J. Moskowitz, Gunjan Shah, Heiko Schöder, Nivetha Ganesan, Helen Hancock, Theresa Davey, Leslie Perez, Samia Sohail, Alayna Santarosa, Charisse Capadona, Brittney Munayirji, Anita Kumar, Oscar Lahoud, Connie Batlevi, Paul Hamlin, David J. Straus, Colette Owens, Philip Caron, Andrew Intlekofer, Audrey Hamilton, Steven Horwitz, Lorenzo Falchi, William Johnson, Lia Palomba, Ariela Noy, Matthew Matasar, Georgios Pongas, Gilles Salles, Santosha Vardhana, Beatriz Wills Sanin, Joachim Yahalom, Ahmet Dogan, Andrew Zelenetz, Craig H. Moskowitz
Journal: HemaSphere (2022)

Figure 1: Progression-free survival for patients enrolled onto part I of the phase II study evaluating P-GVD followed by consideration for HDT/AHCT. 36 pts underwent HDT/AHCT. 2 pts declined transplant and were censored after 2 and 3 months. Introduction/Methods: The standard approach for relapsed or refractory (RR) classical Hodgkin lymphoma (cHL) following front-line treatment failure is second line therapy (SLT) aimed to achieve complete response (CR), followed by consolidation with high dose therapy and autologous hematopoietic cell transplantation (HDT/AHCT). We previously reported results from part I of a phase II study evaluating SLT with pembrolizumab, gemcitabine, vinorelbine, and liposomal doxorubicin (P-GVD) followed by HDT/AHCT (Moskowitz, et al. JCO 2021). We are now enrolling onto part II in which patients with CR after 4 cycles of P-GVD proceed to 13 cycles of pembrolizumab maintenance rather than HDT/AHCT. We present here extended follow-up from part I as well as updated efficacy and toxicity data for P-GVD from parts I (n=39) and II (n=33). Results: Part I included 39 pts evaluable for toxicity and 38 evaluable for efficacy. Among 38 evaluable pts, CR and overall response rates (ORR) were 95% and 100%. 36 pts proceeded to HDT/AHCT, of whom 13 (36%) received post-transplant brentuximab vedotin (BV) (n=12) or BV plus nivolumab (bv/nivo) (n=1) maintenance. After a median follow-up of 30 (range: 2–43) months, 1 pt experienced progression 23 months after transplant. The estimated 30-month progression-free survival (PFS) is 96% (Figure 1). To date, all 33 pts enrolled to part II are evaluable for toxicity and 30 pts for response to P-GVD. Among those, 27 (90%) achieved CR (including 2 with PET-avid findings that were biopsy negative) and 3 (10%) achieved partial response. Among 68 pts evaluable for response from parts I and II, CR and ORR rates were 92.6% and 100%. Among 72 pts evaluable for toxicity, grade 4 or 5 events included grade 4 sepsis (n=1) and grade 5 pneumonitis (n=1, occurred after 4 cycles of P-GVD, pt enrolled on part II). Grade 3 events occurring in >1 pt included neutropenia (n=9, 12.5%), elevated AST/ALT (n=7, 10%), mucositis (n=5, 7%), anemia (n=4, 5%), lung infection (n=2, 3%), and rash (n=2, 3%). Conclusion: Second-line therapy with P-GVD is highly effective and efficiently bridges pts with RR cHL to HDT/AHCT. With extended follow-up for transplanted pts, remissions remain durable with estimated 30-month PFS of 96%. Among 68 evaluable pts enrolled onto parts I and II, CR rate remains high at 92.6%. Enrollment onto part II, which is assessing the role of pembrolizumab maintenance as an alternative to HDT/AHCT for patients in CR, is ongoing.